可穿戴式汗液传感器

News &Highlights
Wearable Elizabeth K.Senior Technology Writer
sors could take the place of invasive blood draws.They might ana-lyze creatinine,to assess kidney function,or cortisol,to track the stress response.Wearable sweat sensing devices could potentially allow continuous biomonitoring,eliminating the need for bulky equipment,repeat visits to labs,or hospital stays.
Recently,an international team led by John A.Rogers,the direc-tor of the Center for Bio-Integrated Electronics at Northwestern University,unveiled what may be the most sophisticated proto-type sweat sensor developed to date (Fig.1).The device not only monitors lactate,glucose,chloride,and pH,but also sweat rate and loss [1].The ability to measure these last two parameters is particularly novel,and crucial for understanding their effects on the composition of sweat samples.
The Rogers group’s device features a flexible elastomeric system of microfluidic channels,valves,and chambers that are removable and can be swapped out for new ones,enabling reuse.The natural action of sweat glands pumps sweat through holes in the bottom of the device into the channels and analysis chambers,each contain-ing a sensor for a different substance.While enzymes in biofuel cell-based,electrochemical sensors catalyze reactions that increase with concentration to assess lactate and glucose levels,the device measures chloride and pH colorimetrically by comparison to color calibration markings.The device transmits and receives data to and
from the same cell phone that powers it via near-field communica-tion (NFC)ing this external power source makes the patch up to 20times lighter and four times smaller than devices that rely on batteries.
Other labs take different approaches.At the California Institute of Technology (Caltech),medical engineering assistant professor Wei Gao and his team believe sweat can be used for many compli-cated analyses involving substances such as heavy metals,drug molecules,and hormones and other proteins.Before moving to Cal-tech,Gao was a postdoctoral fellow in the laboratory of engineer-ing professor Ali Javey at University of California,Berkeley (UC Berkeley),where he helped develop a wearable sensor for caffeine as a model for detecting methylxanthine drugs [2].Unlike the devices powered via NFC,the Gao lab’s prototypes use tiny batter-ies.For some continuous monitoring applications,Gao said,staying close to a cell phone may not be practical.
Yet another team,headed by Hong Liu at Southeast University in Nanjing,recently designed a wearable glucose sweat sensor that,unlike the Rogers’device,does not rely on enzymes [3].These biomolecular components present a number of issues for sensor development.For example,enzymes are sensitive to pH,tempera-ture,and ionic strength;they can degrade over time;and the
1.Developed by an international team of collaborators,this prototype,battery-sweat sensor can monitor lactate,glucose,chloride,pH,and sweat rate and loss.sensor wirelessly transmits and receives data to and from the same cell phone that powers it by via near-field communication (NFC)technology.Credit:John Rogers,Northwestern University.
process of attaching them to electrodes can affect their activity. The Liu group’s sensor,usingfluorocarbon-coated gold electrodes, measures current generated during the electrochemical oxidation of glucose.
Even though thefield is nascent,the potential of wearable sweat sensors has already attracted the attention of companies such as Gatorade.The company’s Sports Science Institute is collaborating with the Rogers’lab and the United States Air Force to test a wearable sweat sensor that measures hydration via electrolyte concentrations[4].Through his company Epicore Biosystems, Rogers is also working with the skin care company L’Oreal to devel-oping a wearable skin pH sensor that can detect unbalanced skin pH levels linked to conditions such as dryness and eczema.L’Oreal and its skincare brand La Roche-Posay unveiled the investigational device,called My Skin Track pH,at the huge annual Consumer Electronics Show in Las Vegas in January2019.The company plans to have the prototype tested by dermatologists this year[5].
But commercial applications may take some time to be realized.In pursuing wearable sweat sensors,developers have taken on two inextricably linked challenges,of engineering and biology.Because the sophisticated technology needed to begin reliably analyzing sweat has only recently been achieved,the scientific study of sweat has just begun,said Gao’s mentor UC Berkeley professor Javey,who co-directs the university’s Sensor and Actuator Center.‘‘Sweat is a highly under-explored class of biofluid,”Rogers agreed.
Addressing the biology part of the challenge is not simple.Sweat rates affect biomarker concentrations,and biomarkers in sweat vary from person to person,changing daily or even hourly,all of which makes it difficult to correlate sweat-excreted biomolecules with health.In addition,not all biomolecule concentrations in sweat correlate well with those in blood.Much more research is needed,involving hundreds or even thousands of human subjects, before definitive claims can be made about sweat and health[6,7].
Key to these biological studies,however,will be continued advances in wearable sensor engineering.For example,Eccrine Systems,a company co-founded by Jason Heikenfeld,the head of the Novel Device Lab at the University of Cincinnati,is working with technology covered by the university’s2018patent for sen-sors that can correlate measurements of substances in sweat with the time the substances were collected[8,9].The invention enables researchers to generate sweat pharmacokinetic profiles,a critical step for ensuring sensor reliability.
All this research activity suggests that wearable sweat sensors have great promise to become important medical and consumer devices,although it is early and likely that different applications will require different types of sensors.‘‘At this stage,we need to explore any and all of these techniques,”Javey said.
References
[1]Bandodkar AJ,Gutruf P,Choi J,Lee KH,Sekine Y,Reeder JT,et al.Battery-free,
skin-interfaced microfluidic/electronic systems for simultaneous electrochemical,colorimetric,and volumetric analysis of sweat.Sci Adv 2019;5(1):eaav3294.
[2]Tai LC,Gao W,Chao M,Bariya M,Ngo QP,Shahpar Z,et al.Methylxanthine drug
monitoring with wearable sweat sensors.Adv Mat2018;30(23):1707442. [3]Zhu X,Ju Y,Chen J,Liu D,Liu H.Nonenzymatic wearable sensor for
electrochemical analysis of perspiration glucose.ACS Sensors2018;3
(6):1135–41.
[4]Sumra H.Gatorade’s sweat-reading hydration wearable is almost ready for
prime time[Internet].London:Wareable Ltd.;2018Mar20[cited2019Mar20].
Available from:https:///wearable-tech/gatorade-sweat-hydration-wearable-2019.
[5]Lugmayr L.CES2019healthcare wearable:L’Oreal My Skin Track pH breaks
cover[Internet].Wearable Technologies;2019Jan8[cited2019Mar6].
Available from:https:///2019/01/ces-2019-healthcare-wearable-loreal-my-skin-track-ph-breaks-cover/.
[6]Bariya M,Nyein HYY,Javey A.Wearable sweat sensors.Nat Electron
2018;1:160–71.
[7]Brothers MC,DeBrosse M,Grigsby CC,Naik RR,Hussain SM,Heikenfeld J,et al.
Achievements and challenges for real-time sensing of analytes in sweat within wearable platforms.Acc Chem Res2019;52(2):297–306.
[8]CincyTech.Wearable sweat sensor pioneer issued key device patent[Internet].
Washington,DC:EurekAlert!/AAAS;2018Dec18[cited2019Mar6].Available from:https:///pub_releases/2018-12/c-wss121818.php. [9]Heikenfeld JC,inventor;University of Cincinnati,assignee.Sweat sensing with
chronological assurance.United States patent US10136831B2.2018Nov27.
360 E.K.Wilson/Engineering5(2019)359–360
Engineering 2 (2016) xxx–xxx
News & Highlights
可穿戴式汗液传感器
Elizabeth K. Wilson
Senior Technology Writer
汗液和血液一样含有电解质和生物分子，可以揭示人类从水合作用到肾功能的各方面生理状况。

尽管科学家们早已认识到汗液可能能够作为一种医学诊断工具，但直到最近，工程技术的进步才使他们得以认真探索这种可能性。

如今，由于芯片实验室和手机数据传输等技术的进步，以及追踪心率或血氧水平的可穿戴设备逐步变得完善和普遍，有关汗液传感器的想法引起了公众的兴趣。

2015年以来，世界各地的工程师们探索了各种不同的设计方法，因此，关于汗液传感器的同行评议论文数量开始激增。

新的汗液传感器原型是附着在手臂或前额上的轻薄贴片，可以测量皮肤的pH 值或氯离子水平，这对遗传性疾病囊性纤维化的诊断很重要。

其他可能的设备还包括为运动员准备的腕带或发带，利用这些设备可以记录运动员在运动过程中体内的水分变化。

在更复杂的医学应用中，可穿戴式汗液传感器可以取代有创抽血。

它们可以分析肌酐，评估肾功能或皮质醇，以跟踪应激反应。

可穿戴式汗液传感器设备有可能实现持续性的生物监测，消除对笨重设备的需求，从而使人们不再需要重复去实验室或住院。

最近，美国西北大学生物集成电子中心（the Center for Bio-Integrated Electronics at Northwestern University ）主任John A. Rogers 领导的国际研究小组公布了可能是迄今为止最复杂的汗液传感器原型（图1）。

该设备不仅能监测乳酸、葡萄糖、氯离子浓度和pH 值，还可以监测出汗速率和出汗量[1]。

利用该设备测量后两个参数
的功能特别新颖，且对研究其对汗液样本组成的影响至关重要。

Rogers 小组的设备具有一个灵活的弹性系统，该系统由微流体通道、阀门和腔体组成，可拆卸、可更换，从而实现重复使用。

汗腺的自然作用可将汗液通过设备底部的小孔泵入通道和分析室，每个通道和分析室都装有针对不同成分的传感器。

在该设备中，电化学传感器是基于生物燃料电池的，用于测量催化反应中酶浓度的增加量，从而评估乳酸和葡萄糖的含量。

该设备通过与颜色校正标记的比较，以比色法来测量氯离子浓度和pH 值。

该设备通过近距离无线通信（near-field communication ，NFC ）技术向为其供电的同一部手机发
送和接收数据。

使用这种外部电源使该设备的重量变为
Contents lists available at ScienceDirect
Engineering
图1. 这款由一个国际合作团队研发的无电池汗液传感器原型可以监测
乳酸、葡萄糖、氯离子浓度、pH 值、出汗速率和出汗量。

该传感器通过近距离无线通信技术，在同一部手机之间无线传输和接收数据。

资料来源：John A. Rogers, Northwestern University 。

401 Author name et al. / Engineering 2(2016) xxx–xxx
依赖电池的设备重量的1/20，体积变为依赖电池的设备体积的1/4。

其他实验室会采用不同的方法。

加州理工学院（California Institute of Technology，Caltech）医学工程副教授Wei Gao和他的团队认为，汗液可以被用于许多复杂的分析，如重金属、药物分子、激素和其他蛋白质等物质。

在到加州理工学院工作之前，Wei Gao是加州大学伯克利分校（University of California, Berkeley，UC Berkeley）工程学教授Ali Javey实验室的博士后研究员。

在那里，他帮助开发了一种可穿戴式咖啡因传感器，这是一种检测甲基黄嘌呤药物的模型[2]。

与通过NFC供电的设备不同，Wei Gao实验室的样机使用的是微型电池。

Wei Gao说，对于一些连续监测应用程序来说，始终保持靠近手机的状态可能不太现实。

然而，由我国东南大学刘宏领导的另一个团队最近设计了一种可穿戴式葡萄糖汗液传感器。

与Rogers小组的设备不同，这种传感器不依赖于酶[3]。

这些生物分子成分为传感器的发展带来了许多问题。

例如，酶对pH值、温度和离子强度十分敏感；酶会随着时间降解；将酶附着在电极上的过程会影响它们的活性。

刘宏团队的传感器使用氟碳涂层金电极，测量了葡萄糖电化学氧化过程中产生的电流。

虽然这个领域目前处于初期阶段，但可穿戴式汗液传感器的潜在商机已经吸引了佳得乐（Gatorade）等公司的注意。

该公司的运动科学研究所（Sports Science Institute）正在与Rogers实验室和美国空军（United States Air Force）合作，测试一种可穿戴式汗液传感器，该传感器可以通过电解质浓度测量水合作用[4]。

Rogers 还通过他的公司Epicore Biosystems与护肤品公司欧莱雅（L’Oreal）合作，开发一种可穿戴式皮肤pH传感器，可以检测与干燥和湿疹等情况有关的皮肤pH值失衡水平。

L’Oreal及其护肤品牌La Roche-Posay于2019年1月在拉斯维加斯举行的大型年度消费者电子产品展（Consumer Electronics Show）上发布了这款名为My Skin Track pH 的新设备。

该公司计划今年让皮肤科医生对这款产品进行测试[5]。

但是商业应用的实现可能需要一定时间。

在研发可穿戴式汗液传感器的过程中，开发人员面临着工程学和生物学这两个无法逃避的问题。

Wei Gao的导师、加州大学伯克利分校传感器和执行机构中心（Sensor and Actuator Center）的联合负责人Javey教授表示，开始可靠地分析汗液所需的复杂技术是最近才实现的，因此对汗液的科学研究才刚刚开始。

“汗液是一种高度未被开发的生物流体”，Rogers表示同意这一观点。

解决生物学方面的问题并不简单。

出汗速率会影响生物标志物的浓度，而汗液中的生物标志物因人而异，每天甚至每小时都在变化，所有汗液排泄的生物分子都难以与健康相关联。

此外，汗液中并非所有的生物分子浓度都与血液中的生物分子浓度密切相关。

关于这方面的问题，还需要更多的研究以及数百甚至数千个人类受试者，才能对汗液和健康做出明确的判断[6,7]。

然而，这些生物学研究的重点将会使可穿戴式传感器工程持续发展。

例如，美国辛辛那提大学（University of Cincinnati）新型设备实验室（Novel Device Lab）负责人Jason Heikenfeld与Eccrine Systems公司，正在使用该大学2018年专利所涉及的传感器技术，该技术可以将汗液中物质的测量结果与收集物质的时间关联起来[8,9]。

这一发明能够使研究人员绘制出汗液的药代动力学曲线，这是确保传感器可靠性的关键步骤。

所有的这些研究活动都表明，可穿戴式汗液传感器有望成为重要的医疗和消费设备。

尽管这还为时尚早，而且不同的应用可能需要不同类型的传感器，但Javey 表示，“在这个阶段，我们需要探索所有这些技术。

”Reference
[1] Bandodkar AJ, Gutruf P, Choi J, Lee KH, Sekine Y, Reeder JT, et al. Battery-
free, skin-interfaced microfluidic/electronic systems for simultaneous electrochemical, colorimetric, and volumetric analysis of sweat. Sci Adv 2019;5(1):eaav3294.
[2] Tai LC, Gao W, Chao M, Bariya M, Ngo QP, Shahpar Z, et al. Methylxanthine
drug monitoring with wearable sweat sensors. Adv Mat 2018;30(23):1707442.
[3] Zhu X, Ju Y, Chen J, Liu D, Liu H. Nonenzymatic wearable sensor for
electrochemical analysis of perspiration glucose. ACS Sensors 2018;3
(6):1135–41.
[4] Sumra H. Gatorade’s sweat-reading hydration wearable is almost ready for
prime time [Internet]. London: Wareable Ltd.; 2018 Mar 20 [cited 2019 Mar 20]. Available from: https:///wearable-tech/gatorade-sweathydration-wearable-2019.
[5] Lugmayr L. CES 2019 healthcare wearable: L’Oreal My Skin Track pH breaks
cover [Internet]. Wearable Technologies; 2019 Jan 8 [cited 2019 Mar 6].
Available from: https:///2019/01/ces-2019healthcare-wearable-loreal-my-skin-track-ph-breaks-cover/.
[6] Bariya M, Nyein HYY, Javey A. Wearable sweat sensors. Nat Electron
2018;1:160–71.
[7] Brothers MC, DeBrosse M, Grigsby CC, Naik RR, Hussain SM, Heikenfeld J, et
al. Achievements and challenges for real-time sensing of analytes in sweat within wearable platforms. Acc Chem Res 2019;52(2):297–306.
[8] CincyTech. Wearable sweat sensor pioneer issued key device patent [Internet].
Washington, DC: EurekAlert!/AAAS; 2018 Dec 18 [cited 2019 Mar 6]. Available from: https:///pub_releases/2018-12/c-wss121818.php. [9] Heikenfeld JC, inventor; University of Cincinnati, assignee. Sweat sensing with
chronological assurance. United States patent US 10136831B2. 2018 Nov 27.。